DESCRIPTION (Adapted from the application): Pulmonary hypertension is a major cause of morbidity and mortality in septic shock. Current treatment regimens to reduce pulmonary blood pressure, which utilize gaseous nitric oxide, are cumbersome, expensive, and involve potentially toxic exposure to health care personnel. The recent development of a novel class of selective pulmonary vasodilators, which are based on highly charged polar NO adducts, promises to revolutionize the treatment of pulmonary hypertension secondary to septic shock. Inotek now proposes to establish proof-of-principle utilizing its lead compound, DMAEP/NO, in an ovine model of live Pseudomonas induced septic shock. Upon confirmation that DMAEP/NO reverses pulmonary hypertension in this stringent and clinically relevant experimental model, Inotek intends to apply for Phase II SBIR funding to support formal toxicology and a Phase I FDA-regulated clinical trial. PROPOSED COMMERCIAL APPLICATION: There is no convenient, safe and inexpensive treatment for sepsis induced pulmonary hypertension. Estimated worldwide gross sales of Inotek's novel compound are $500 million per annum, 4 years after market entry.